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Alternative Splicing and Aging

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Clinical Genetics and Genomics of Aging

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Abstract

One of the main processes involved in genetic expression is the so-called splicing in which the introns present in the precursor messenger RNA are removed, and exons are joined together, forming the mature form of mRNA. Such a process gives quite a versatility and plasticity to the genome since it can generate different mRNA isoforms from a single pre-mRNA through a process known as alternative splicing (AS). AS is a mechanism through which a higher level of complexity can be achieved, despite the relatively limited capacity of the coding transcriptome. Humans (Homo sapiens), compared to other model organisms, have a higher percentage of AS events. Aberrant splicing events have been correlated with several diseases including those correlated to age, since most of them lead to aberrant protein formation and, therefore, to misfolded protein accumulation, a process very common in these types of diseases. In this context, AS seems to be a critical process not only for therapeutic purposes but also to deeply understand the pathophysiology of diseases. Therefore, in the present chapter, we resume the main characteristics of AS and review its relationship with some of the primary age-related diseases.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

AS:

Alternative splicing

BPS:

Branch point site

BS:

Bloom syndrome

CTD:

C-terminal domain (CTD)

DMD:

Duchenne muscular dystrophy

ESE:

Exonic splicing enhancer

ESS:

Exonic splicing silencer

HAT:

Histone acetylase

HDAC:

Histone deacetylase

HGS:

Hutchinson-Gilford syndrome

hnRNP:

Heterogeneous nuclear ribonucleoprotein

ISE:

Intronic splicing enhancer

ISS:

Intronic splicing silencer

NMD:

Nonsense-mediated mRNA decay

PD:

Parkinson’s disease

pre-mRNA:

Precursor messenger mRNA

PTC:

Premature termination codons

RNAPII:

RNA polymerase II

snRNA:

Small nuclear RNA

snRNP:

Small nuclear ribonucleoprotein

SR:

Serine-arginine-rich proteins

SS:

Splice sites

WS:

Werner syndrome

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Authors and Affiliations

  1. Departamento de Ecología Funcional, Instituto de Ecología, UNAM, Mexico City, Mexico

    J. C. Yustis-Rubio

  2. División de Ciencias Básicas, Instituto Nacional de Geriatría (INGER), Mexico City, Mexico

    Juan Carlos Gomez-Verjan

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  1. J. C. Yustis-Rubio
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  2. Juan Carlos Gomez-Verjan
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Correspondence to Juan Carlos Gomez-Verjan .

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Editors and Affiliations

  1. Basic Sciencies Division, National Institute of Geriatrics, Ciudad de México, Mexico

    Juan Carlos Gomez-Verjan

  2. Instituto Nacional de Geriatría (INGER), Ciudad de México, Mexico

    Nadia Alejandra Rivero-Segura

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Yustis-Rubio, J.C., Gomez-Verjan, J.C. (2020). Alternative Splicing and Aging. In: Gomez-Verjan, J., Rivero-Segura, N. (eds) Clinical Genetics and Genomics of Aging. Springer, Cham. https://doi.org/10.1007/978-3-030-40955-5_7

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